Regulatory roles of IL-12, IL-4 and IFN-gamma on IgE synthesis in atopic patients

Objective To investigate the mechanism of cytokine regulation in atopy by a nalyzing the effects of three major cytokines, IL-4, IL-12 and IFN-gamma on in vitro IgE synthesis of human peripheral blood mononuclear cell (PBMC) f rom normal individuals and atopic patients. Methods We investigated 5 normal individuals and 22 atopic patients includi ng 12 allergic asthma, 8 allergic rhinitis and 2 atopic dermatitis. Human P BMCs were separated and incubated in 96-wells culture plates with different cytokines. Cultured for 7 days, the supernatant was collected and the cont ents of IgE synthesized in vitro were detected. Results There was no IgE synthesis in vitro of PBMC from all the normal ind ividuals and 7 patients, however, of her 15 patients' PBMC could produce Ig E in vitro. We found that rhIL-4 could induce in vitro IgE synthesis of PBM C from ail the normal individuals and 22 patients. rhIL-12 could inhibit Ig E synthesis induced by rhIL-4. Further investigation of cytokine effects on IgE synthesis was conducted in 15 patients whose PBMCs did produce IgE in vitro (average level was 714 +/- 1105 ng/L). The following effects were obs erved: (1) 10 mu g/L rhIL-4 could augment in vitro IgE synthesis from 714 /- 1105 ng/L to higher level of 1483 +/- 1396 ng/L; (2) 20 mu g/L rhIL-12 c ould inhibit in vitro IgE synthesis from 714 +/- 1105 ng/L to lower level o f 452 +/- 969 ng/L; (3) rhIL-12 could block IgE synthesis induced by rhIL-4 to the level of 583 +/- 1084 ng/L; (4) 50 mu g/L IFN-gamma could inhibit i n vitro IgE synthesis from 714 rt 1105 ng/L to the level of 461 +/- 1063 ng /L. Conclusions rhIL-4 could induce in vitro IgE synthesis, rhIFN-gamma could i nhibit the in vitro IgE synthesis and rhIL-12 could antagonize rhIL-4 effec t on in vitro IgE synthesis of PBMC from atopic patients.